Solid State Machinery of Multiple Dynamic Elements in a Metal-Organic Framework.

Engineering coordinated rotational motion in porous architectures enables the fabrication of molecular machines in solids. A flexible two-fold interpenetrated pillared Metal-Organic Framework precisely organizes fast mobile elements such as bicyclopentane (BCP) (107  Hz regime at 85 K), two distinct pyridyl rotors and E-azo group involved in pedal-like motion. Reciprocal sliding of the two sub-networks, switched by chemical stimuli, modulated the sizes of the channels and finally the overall dynamical machinery. Actually, iodine-vapor adsorption drives a dramatic structural rearrangement, displacing the two distinct subnets in a concerted piston-like motion. Unconventionally, BCP mobility increases, exploring ultra-fast dynamics (107  Hz) at temperatures as low as 44 K, while the pyridyl rotors diverge into a faster and slower dynamical regime by symmetry lowering. Indeed, one pillar ring gained greater rotary freedom as carried by the azo-group in a crank-like motion. A peculiar behavior was stimulated by pressurized CO2, which regulates BCP dynamics upon incremental site occupation. The rotary dynamics is intrinsically coupled to the framework flexibility as demonstrated by complementary experimental evidence (multinuclear solid-state NMR down to very low temperatures, synchrotron radiation XRD, gas sorption) and computational modelling, which helps elucidate the highly sophisticated rotor-structure interplay.

Does It Matter What Screener We Use? A Comparison of Ultra-brief PHQ-4 and E-mwTool-3 Screeners for Anxiety and Depression Among People With and Without HIV.

The burden of depression and anxiety disorders is high in sub-Saharan Africa, especially for people with HIV (PWH). The Patient Health Questionnaire-4 (PHQ-4) and Electronic Mental Wellness Tool-3 (E-mwTool-3) are ultra-brief screening tools for these disorders. We compared the performance of PHQ-4 and E-mwTool-3 for screening MINI-International Neuropsychiatric Interview diagnoses of depression and anxiety among a sample of individuals with and without HIV in two primary care clinics and one general hospital in Maputo City, Mozambique. Areas-under-the-curve (AUC) were calculated along with sensitivities and specificities at a range of cutoffs. For PWH, at a sum score cutoff of ≥ 1, sensitivities were strong: PHQ-4:Depression = 0.843; PHQ-4:Anxiety = 0.786; E-mwTool-3:Depression = 0.843; E-mwTool-3:Anxiety = 0.929. E-mwTool-3 performance was comparable to PHQ-4 among people with and without HIV.

Benchmark Dynamics of Dipolar Molecular Rotors in Fluorinated Metal-Organic Frameworks.

Fluorinated Metal-Organic Frameworks (MOFs), comprising a wheel-shaped ligand with geminal rotating fluorine atoms, produced benchmark mobility of correlated dipolar rotors at 2 K, with practically null activation energy (Ea =17 cal mol-1 ). 1 H T1 NMR revealed multiple relaxation phenomena due to the exchange among correlated dipole-rotor configurations. Synchrotron radiation X-ray diffraction at 4 K, Density Functional Theory, Molecular Dynamics and phonon calculations showed the fluid landscape and pointed out a cascade mechanism converting dipole configurations into each other. Gas accessibility, shown by hyperpolarized-Xe NMR, allowed for chemical stimuli intervention: CO2 triggered dipole reorientation, reducing their collective dynamics and stimulating a dipole configuration change in the crystal. Dynamic materials under limited thermal noise and high responsiveness enable the fabrication of molecular machines with low energy dissipation and controllable dynamics.

Cascade Dynamics of Multiple Molecular Rotors in a MOF: Benchmark Mobility at a Few Kelvins and Dynamics Control by CO2.

Achieving sophisticated juxtaposition of geared molecular rotors with negligible energy-requirements in solids enables fast yet controllable and correlated rotary motion to construct switches and motors. Our endeavor was to realize multiple rotors operating in a MOF architecture capable of supporting fast motional regimes, even at extremely cold temperatures. Two distinct ligands, 4,4'-bipyridine (bipy) and bicyclo[1.1.1]pentanedicarboxylate (BCP), coordinated to Zn clusters fabricated a pillar-and-layer 3D array of orthogonal rotors. Variable temperature XRD, 2H solid-echo, and 1H T1 relaxation NMR, collected down to a temperature of 2 K revealed the hyperfast mobility of BCP and an unprecedented cascade mechanism modulated by distinct energy barriers starting from values as low as 100 J mol-1 (24 cal mol-1), a real benchmark for complex arrays of rotors. These rotors explored multiple configurations of conrotary and disrotary relationships, switched on and off by thermal energy, a scenario supported by DFT modeling. Furthermore, the collective bipy-ring rotation was concerted with the framework, which underwent controllable swinging between two arrangements in a dynamical structure. A second way to manipulate rotors by external stimuli was the use of CO2, which diffused through the open pores, dramatically changing the global rotation mechanism. Collectively, the intriguing gymnastics of multiple rotors, devised cooperatively and integrated into the same framework, gave the opportunity to engineer hypermobile rotors (107 Hz at 4 K) in machine-like double ligand MOF crystals.

Direct in Situ Crystallographic Visualization of a Dual Mechanism for the Uptake of CO2 Gas by a Flexible Metal-Organic Framework.

We report a flexible metal-organic framework, [Co2(OBA)2(BPMP)] n (COB), with a new network topology. COB displays structural flexibility under CO2 gas pressure at 298 K, and the resultant porous phases have been characterized by in situ X-ray diffraction analysis. We show that activation yields a framework with discrete voids and substantial reduction in guest-accessible volume. Single-crystal X-ray diffraction analysis under controlled CO2 pressure shows that COB exhibits a breathing mode of flexibility, combined with an overall swelling of the framework. This combination of mechanisms is highly unusual.

Tight Xenon Confinement in a Crystalline Sandwich-like Hydrogen-Bonded Dimeric Capsule of a Cyclic Peptide.

A cyclic hexapeptide with three pyridyl moieties connected to its backbone forms a hydrogen-bonded dimer, which tightly encapsulates a single xenon atom, like a pearl in its shell. The dimer imprints its shape and symmetry to the captured xenon atom, as demonstrated by 129 Xe NMR spectroscopy, single-crystal X-ray diffraction, and computational studies. The dimers self-assemble hierarchically into tubular structures to form a porous supramolecular architecture, whose cavities are filled by small molecules and gases.

Solvent- and Pressure-Induced Phase Changes in Two 3D Copper Glutarate-Based Metal-Organic Frameworks via Glutarate (+gauche ⇄ -gauche) Conformational Isomerism.

Two isoreticular three-dimensional copper(II) glutarate-based pillared-layered metal-organic frameworks (MOFs) with flexible pillars, [Cu2(glu)2(bpa)] and [Cu2(glu)2(bpp)] (bpa = 1,2-bis(4-pyridyl)ethane; bpp = 1,3-bis(4-pyridyl)propane), undergo spontaneous phase changes upon solvent loss at room temperature. Using single-crystal X-ray diffraction analysis (SCXRD), we show that the phase changes result in new narrow-channel forms that experience a large reduction in solvent-accessible volume. Moreover, the [Cu2(glu)2(bpa)] MOF displays a stepped sorption isotherm for the uptake of CO2 at room temperature. This is indicative of reversion of the framework to the wide-channel form under CO2 pressure. Supercritical CO2 was used to isolate the gas-included structures, and by means of SCXRD we were able to determine the positions of the CO2 molecules in the channels of the frameworks. Finally, we report the use of molecular modeling simulations to elucidate the phase-change mechanism, including the energetic changes involved. Structural limitations in both MOFs allow for only direct gauche-gauche enantiomeric interconversion of the glutarate moieties.

Activation-Dependent Breathing in a Flexible Metal-Organic Framework and the Effects of Repeated Sorption/Desorption Cycling.

A non-interpenetrated metal-organic framework with a paddle-wheel secondary building unit has been activated by direct thermal evacuation, guest exchange with a volatile solvent, and supercritical CO2 drying. Conventional thermal activation yields a mixture of crystalline phases and some amorphous content. Exchange with a volatile solvent prior to vacuum activation produces a pure breathing phase with high sorption capacity, selectivity for CO2 over N2 and CH4 , and substantial hysteresis. Supercritical drying can be used to access a guest-free open phase. Pressure-resolved differential scanning calorimetry was used to confirm and investigate a systematic loss of sorption capacity by the breathing phase as a function of successive cycles of sorption and desorption. A corresponding loss of sample integrity was not detectable by powder X-ray diffraction analysis. This may be an important factor to consider in cases where flexible MOFs are earmarked for industrial applications.

Giant Hysteretic Sorption of CO2 : In Situ Crystallographic Visualization of Guest Binding within a Breathing Framework at 298 K.

A dynamic ZnII -MOF has been shown to exhibit extreme breathing behavior under gas pressure. The very narrow pore form of the activated framework opens up in the presence of carbon dioxide, thus making it a suitable material for CO2 capture. Sorption of CO2 at 298 K and relatively high pressure clearly shows a two-step isotherm with giant hysteresis for the second step. In-situ single-crystal diffraction analysis was carried out under CO2 gas pressure at 298 K using an environmental gas cell in order to visualize the interaction between CO2 and the host framework. The results are well supported by pressure-gradient differential scanning calorimetry (P-DSC) and variable-pressure powder X-ray analysis. Theoretical calculations have been carried out in order to further back up the crystallographic data.

Extreme carbon dioxide sorption hysteresis in open-channel rigid metal-organic frameworks.

A systematic study is presented of three closely related microporous metal-organic frameworks the pore dimensions of which vary according to the choice of 4,4'-bipyridyl linker. The tunable linker allows exploration of the effect of increasing pore dimensions on the sorption behavior of the frameworks. The MOFs described capture CO2 under supercritical conditions and continue to sequester the gas under ambient conditions. Gas sorption isotherms for CO2 are compared with thermogravimetric data, and the CO2 molecules in the channels of the frameworks could be modeled using single-crystal X-ray diffraction analysis. Crystallographic data were used to construct a theoretical model based on DFT methods to calculate framework electrostatic potential maps with a view to understanding the nature of the sorbate-sorbent interactions.

Direct evidence for single-crystal to single-crystal switching of degree of interpenetration in a metal-organic framework.

A known doubly interpenetrated metal-organic framework with the formula [Zn2(ndc)2(bpy)] possesses minimal porosity when activated. We show not only that the material converts to its triply interpenetrated analogue upon desolvation, but also that the transformation occurs in a single-crystal to single-crystal manner under ambient conditions. The mechanism proposed for the conversion is supported by computational methods and by analogy with the solid-state behavior of an analogous system.

In-home TB Testing Using GeneXpert Edge is Acceptable, Feasible, and Improves the Proportion of Symptomatic Household Contacts Tested for TB: A Proof-of-Concept Study.

Background: Household contact investigations are effective for finding tuberculosis (TB) cases but are hindered by low referral uptake for clinic-based evaluation and testing. We assessed the acceptability and feasibility of in-home testing of household contacts (HHC) using the GeneXpert Edge platform. Methods: We conducted a 2-arm, randomized study in Eastern Cape, South Africa. HHCs were verbally assessed using the World Health Organization-recommended 4-symptom screen. Households with ≥1 eligible symptomatic contact were randomized. Intervention households received in-home GeneXpert MTB/RIF molecular testing. GeneXpert-positive HHCs were referred for clinic-based treatment. Standard-of-care households were referred for clinic-based sputum collection and testing. We defined acceptability as agreeing to in-home testing and feasibility as generation of valid Xpert MTB/RIF results. The proportion and timeliness of test results received was compared between groups. Results: Eighty-four households were randomized (n = 42 per arm). Of 100 eligible HHCs identified, 98/100 (98%) provided consent. Of 51 HHCs allocated to the intervention arm, all accepted in-home testing; of those, 24/51 (47%) were sputum productive and 23/24 (96%) received their test results. Of 47 HCCs allocated to standard-of-care, 7 (15%) presented for clinic-based TB evaluation, 6/47 (13%) were tested, and 4/6 (67%) returned for their results. The median (interquartile range) number of days from screening to receiving test results was 0 (0) and 16.5 (11-15) in the intervention and standard-of-care arms, respectively. Conclusions: In-home testing for TB was acceptable, feasible, and increased HHCs with a molecular test result. In-home testing mitigates a major limitation of household contact investigations (dependency on clinic-based referral), revealing new strategies for enhancing early case detection.

Validation of screening instruments for common mental disorders and suicide risk in south African primary care settings.

INTRODUCTION: In South Africa, there is limited mental health infrastructure and resources. Valid screening tools are needed to facilitate identification and linkage to care. We evaluated the performance of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Primary Care Post Traumatic Stress Disorder Screen for DSM-5 (PC-PTSD-5), and the Columbia Suicide Severity Rating Scale (C-SSRS) among adults in South Africa against a diagnostic gold standard. METHODS: Adults present at healthcare facilities were screened with the PHQ-9, GAD-7, PC-PTSD-5, and the C-SSRS. Nurses used a structured diagnostic interview to identify depression, anxiety, panic disorder, PTSD and elevated suicide risk. We assessed the internal consistency, criterion validity, and the sensitivity and specificity of these tools. RESULTS: Of the 1885 participants, the prevalence of common mental disorders and suicide risk was 24.4 % and 14.9 %, respectively. The PHQ-9, GAD-7, and PC-PTSD-5 showed good internal consistency (0.80-0.89). All screeners demonstrated good criterion validity. For depression, a cut-off of ≥5 on the PHQ-9 yielded sensitivity of 84.24 %, while ≥10 yielded sensitivity of 48.77 %. For anxiety, the GAD-7 performed similarly. A cut-off of ≥4 on the PC-PTSD yielded sensitivity of 61.96 %. The C-SSRS yielded lower sensitivity than expected. LIMITATIONS: The prevalence data is not generalizable to the larger South African adult population given the use of a targeted, healthcare facility-based sampling and recruitment strategy. CONCLUSIONS: The performance of the PHQ-9, GAD-7, and PC-PTSD-5 demonstrated good internal consistency and criterion validity, though sensitivity and specificity trade-offs were enhanced with lower cut-offs. Further research into suicide risk screening is warranted.

Validation of a brief screener for broad-spectrum mental and substance-use disorders in South Africa.

In low-resource settings, valid mental health screening tools for non-specialists can be used to identify patients with psychiatric disorders in need of critical mental health care. The Mental Wellness Tool-13 (mwTool-13) is a 13-item screener for identifying adults at risk for common mental disorders (CMDs) alcohol-use disorders (AUDs), substance-use disorders (SUD), severe mental disorders (SMDs), and suicide risk (SR). The mwTool-13 is administered in two steps, specifically, only those who endorse any of the initial three questions receive the remaining ten questions. We evaluated the performance of mwTool-13 in South Africa against a diagnostic gold standard. We recruited a targeted, gender-balanced sample of adults, aged ≥18 years at primary and tertiary healthcare facilities in Eastern Cape Province. Of the 1885 participants, the prevalence of CMD, AUD, SMD, SR, and SUD was 24.4%, 9.5%, 8.1%, 6.0%, and 1.6%, respectively. The mwTool-13 yielded high sensitivities for CMD, SMD, and SR, but sub-optimal sensitivities for AUD and SUD (56.7% and 64.5%, respectively). Including a single AUD question in the initial question set improved the tool's performance in identifying AUD and SUD (sensitivity > 70%), while maintaining brevity, face-validity, and simplicity in the South African setting.

Incremental costs of integrated PrEP provision and effective use counselling in community-based platforms for adolescent girls and young women in South Africa: an observational study.

INTRODUCTION: Adolescent girls and young women (AGYW) are a priority population for pre-exposure prophylaxis (PrEP), a highly effective HIV prevention method. However, effective PrEP use among AGYW has been low. Interventions to support PrEP effective use may improve pill-taking. Affordability of PrEP programs depends on their cost. We, therefore, evaluated the cost of community-based PrEP with effective use counselling. METHODS: Cost data from a randomized controlled trial were used to evaluate the cost of PrEP provision with effective use counselling offered to AGYW through community-based HIV testing platforms between November 2018 and November 2019. AGYW were randomized to receive (1) group-based community health club effective use counselling, (2) individualized effective use counselling or (3) community-based PrEP dispensary. Task shifting of effective use counselling from nurses to trained lay counsellors was implemented in groups 1 and 2. Personnel costs were estimated from time-and-motion observations and staff interviews. Expenditure and ingredients-based approaches were used to estimate costs for medical and non-medical supplies. RESULTS: In total, 603 AGYW initiated PrEP and accrued a total of 1280 months on PrEP. Average cost per person-month on PrEP with group-based community health club, individualized effective use counselling and community-based PrEP dispensary under the Department of Health scenario were similar and high (USD $55.32, $55.65 and $55.46, respectively) due to low PrEP client volume observed in the clinical trial. Increasing client volume (scaled Department of Health scenario) reduced cost per-person month estimates to USD $15.48, $26.40 and $13.99, respectively. CONCLUSIONS: As designed, individualized effective use counselling increased the cost of standard-of-care PrEP delivery by 89%, group-based community health effective use counselling increased the cost of standard-of-care PrEP delivery by 11%. These estimates can inform cost-effectiveness and budget impact analysis for PrEP provision with effective use counselling services.

Sexually transmitted infection screening to prevent adverse birth and newborn outcomes: study protocol for a randomized-controlled hybrid-effectiveness trial.

BACKGROUND: Sexually transmitted infections (STIs) during pregnancy are associated with adverse birth outcomes, including preterm birth, low birth weight, perinatal death, and congenital infections such as increased mother-to-child HIV transmission. Prevalence of STIs among pregnant women in South Africa remains high, with most women being asymptomatic for their infection(s). Unfortunately, most STIs remain undetected and untreated due to standard practice syndromic management in accordance with World Health Organization (WHO) guidelines. Although lab-based and point-of-care molecular tests are available, optimal screening strategies during pregnancy, their health impact, and cost-effectiveness are unknown. METHODS: We will implement a 3-arm (1:1:1) type-1 hybrid effectiveness-implementation randomized-controlled trial (RCT). We will enroll 2500 pregnant women attending their first antenatal care (ANC) visit for their current pregnancy at participating health facilities in Buffalo City Metro District, Eastern Cape Province, South Africa. Participants allocated to arms 1 and 2 (intervention) will receive GeneXpert® point-of-care diagnostic testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis, with same-day treatment for detected infection(s). Arm 1 will additionally receive a test-of-cure 3 weeks post-treatment, while Arm 2 will receive a repeat test at 30-34 weeks' gestation. Those allocated to Arm 3 will receive syndromic management (standard-of-care). The RE-AIM framework will be used to guide collection of implementation indicators to inform potential future scale up. Primary outcome measures include (1) frequency of adverse birth outcomes among study arms, defined by a composite measure of low birth weight and pre-term delivery, and (2) change in STI prevalence between baseline and birth outcome among intervention arms and compared to standard-of-care. Estimates and comparative costs of the different screening strategies relative to standard-of-care and the costs of managing adverse birth outcomes will be calculated. Cost-effectiveness will be assessed per STI and disability-adjusted life year averted. DISCUSSION: This trial is the first RCT designed to identify optimal, cost-effective screening strategies that decrease the burden of STIs during pregnancy and reduce adverse birth outcomes. Demonstrating the impact of diagnostic screening and treatment, compared to syndromic management, on birth outcomes will provide critical evidence to inform changes to WHO guidelines for syndromic management of STIs during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04446611 . Registered on 25 June 2020.

Acceptability and feasibility of leveraging community-based HIV counselling and testing platforms for same-day oral PrEP initiation among adolescent girls and young women in Eastern Cape, South Africa.

INTRODUCTION: Community-based delivery of HIV pre-exposure prophylaxis (PrEP) to South African adolescent girls and young women's (AGYW) could increase access but needs evaluation. We integrated PrEP services via home-based services and pop-up tents into existing community-based HIV testing services (CB-HTS) in Eastern Cape Province, South Africa. METHODS: After accessing CB-HTS via a "pop-up" tent or home-based services, HIV-negative AGYW aged 16-25 years were invited to complete a baseline questionnaire and referred for PrEP services at a community-based PrEP site co-located with pop-up HTS tents. A 30-day supply of PrEP was dispensed. PrEP uptake, time-to-initiation, cohort characteristics and first medication refill within 90 days were measured using descriptive statistics. RESULTS: Of the 1164 AGYW who tested for HIV, 825 (74.3%) completed a questionnaire and 806 (97.7%) were referred for community-based PrEP. Of those, 624 (77.4%) presented for PrEP (482/483 [99.8%] from pop-up HTS and 142/323 [44.0%] from home-based HTS), of which 603 (96.6%) initiated PrEP. Of those initiating PrEP following home-based HTS, 59.1% initiated within 0-3 days, 25.6% within 4-14 days and 15.3% took ≥15 days to initiate; 100% of AGYW who used pop-up HTS initiated PrEP the same day. Among AGWY initiating PrEP, 37.5% had a detectable sexually transmitted infection (STI). Although AGYW reported a low self-perception of HIV risk, post-hoc application of HIV risk assessment measures to available data classified most study participants as high risk for HIV acquisition. Cumulatively, 329 (54.6%) AGYW presented for a first medication refill within 90 days of accepting their first bottle of PrEP. CONCLUSIONS: Leveraging CB-HTS platforms to provide same-day PrEP initiation and refill services was acceptable to AGYW. A higher proportion of AGYW initiated PrEP when co-located with CB-HTS sites compared to those referred following home-based HTS, suggesting that proximity of CB-HTS and PrEP services facilitates PrEP uptake among AGYW. The high prevalence of STIs among those initiating PrEP necessitates the integration of STI and HIV prevention programs for AGYW. Eligibility for PrEP initiation should not be required among AHYW in high HIV burden communities. Community-based service delivery will be crucial to maintaining access to PrEP services during the COVID-19 pandemic and future health and humanitarian emergencies.

Highly luminescent scintillating hetero-ligand MOF nanocrystals with engineered Stokes shift for photonic applications.

Large Stokes shift fast emitters show a negligible reabsorption of their luminescence, a feature highly desirable for several applications such as fluorescence imaging, solar-light managing, and fabricating sensitive scintillating detectors for medical imaging and high-rate high-energy physics experiments. Here we obtain high efficiency luminescence with significant Stokes shift by exploiting fluorescent conjugated acene building blocks arranged in nanocrystals. Two ligands of equal molecular length and connectivity, yet complementary electronic properties, are co-assembled by zirconium oxy-hydroxy clusters, generating crystalline hetero-ligand metal-organic framework (MOF) nanocrystals. The diffusion of singlet excitons within the MOF and the matching of ligands absorption and emission properties enables an ultrafast activation of the low energy emission in the 100 ps time scale. The hybrid nanocrystals show a fluorescence quantum efficiency of ~60% and a Stokes shift as large as 750 meV (~6000 cm-1), which suppresses the emission reabsorption also in bulk devices. The fabricated prototypal nanocomposite fast scintillator shows benchmark performances which compete with those of some inorganic and organic commercial systems.

Mobile technology and task shifting to improve access to alcohol treatment services in Mozambique.

INTRODUCTION: Unhealthy alcohol use (UAU) is a major public health challenge, particularly in low- and middle-income countries. Mozambique is the fourth poorest country in the world where half of the population lives below the poverty line. UAU is frequent among drinkers in Mozambique; however, resources and infrastructure to treat UAU are very limited. This paper examines how task-shifting and a provider-facing mobile health application are being used to improve access to care. In this paper, the feasibility, acceptability and appropriateness of a provider-facing mobile health application being used under a task-shifting model to identify UAU and provide a four-session brief motivational interviewing intervention are described. METHOD: The study used a sequential exploratory mixed-methods design with a QUAL â†’ quan structure. First, 15 psychiatric technicians and primary care providers in Mozambique's Nampula Province participated in semi-structured interviews. These interviews were recorded and transcribed. Then, 45 providers completed a 12-item quantitative survey on tablets. Quantitative analysis used descriptive statistic calculation and qualitative analysis used thematic analysis. RESULTS: Nonspecialized providers found the mobile health app to be acceptable, appropriate, and feasible when delivering a 4-session brief motivational intervention under a task-shifting model. Central benefits of the technology were enhanced standardization and efficiency of sessions as well as feelings of legitimacy when interacting with patients. Main concerns were feasibility of implementing the intervention due to time constraints of workload and internet connectivity issues. CONCLUSIONS: Provider-facing technology shows promise in supporting task-shifting models that can expand alcohol intervention services and increase access to care in low- and middle-income countries. Providers without specialized training in behavioral health interventions can provide critical services to patients with UAU and provider-facing mobile health applications may help bring such models to scale.

Employment preferences of healthcare workers in South Africa: Findings from a discrete choice experiment.

There is a maldistribution of human resources for health globally, with many Lower- and Middle-Income Countries experiencing significant shortages. We examined healthcare workers' job preferences in South Africa to identify factors which potentially influence employment decisions. A discrete choice experiment was conducted among 855 South African healthcare workers critical to its national HIV testing and treatment programs. Job characteristics included workload, workplace culture, availability of equipment, training opportunities, sector and facility type, location, salary and benefits. Main effects analysis was conducted using fixed effects logistic regression. Interaction effects identified divergence in preferences. Heavy workload (OR = 0.78; 95% C.I. 0.74-0.83), poor workplace culture (odds ratio 0.66; 95% C.I. 0.62-0.69), insufficient availability of equipment (OR = 0.67; 95% C.I. 0.63-0.70) and infrequent training opportunities (OR = 0.75; 95% C.I. 0.71-0.80) had large, significant effects on worker preferences. An increase in salary of 20% (OR = 1.29; 95% C.I. 1.16-1.44) had a positive effect on preferences, while a salary decrease of 20% (OR = 0.55; 95% C.I. 0.49-0.60) had a strong negative effect. Benefits packages had large positive effects on preferences: respondents were twice as likely to choose a job that included medical aid, pension and housing contributions worth 40% of salary (OR = 2.06; 95% C.I. 1.87-2.26), holding all else constant. Although salary was important across all cadres, benefits packages had larger effects on job preferences than equivalent salary increases. Improving working conditions is critical to attracting and retaining appropriate health cadres responsible for the country's HIV services, especially in the public sector and underserved, often rural, communities. Crucially, our evidence suggests that factors amenable to improvement such as workplace conditions and remuneration packages have a greater influence on healthcare workers employment decisions than employment sector or location.